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Published on: November 1, 2007
An alkali-soluble factor present in normal brain tissue inhibits antigen-specific lymphocyte proliferation
1Department of Neurology, University of Texas--Houston Medical School, 77030, USA. blindsey@neuro.med.uth.tmc.edu
Insights
Brain tissue contains immune regulatory factors that inhibit lymphocyte proliferation to antigens but stimulate responses to mitogens. This activity, linked to a brain glycoprotein or proteoglycan, warrants further study in vivo.
Area of Science:
- Neuroimmunology
- Cellular immunology
Background:
- The brain is recognized as an immune privileged site.
- It is hypothesized to contain multiple immune regulatory factors.
Purpose of the Study:
- To investigate the immune regulatory properties of brain tissue on cultured lymphocytes.
- To characterize the nature of these regulatory factors.
Main Methods:
- Lymphocyte proliferation assays using homogenized brain tissue.
- Enzymatic (protease, neuraminidase) and chemical (alkali solubility) treatments.
- Gel filtration chromatography.
- Assays for cytokine (IL-2) effects, Fas/FasL interactions, and gangliosides.
Main Results:
- Brain homogenate inhibited antigen-specific lymphocyte proliferation but stimulated mitogen-induced proliferation.
- The inhibitory activity was sensitive to proteases and neuraminidase.
- The active factor was found in the high molecular weight fraction of alkali-soluble brain homogenate, containing protein and carbohydrate.
- This factor blocked the effects of IL-2 and was independent of known regulatory cytokines, Fas/FasL, and gangliosides.
Conclusions:
- A brain-derived glycoprotein or proteoglycan, potentially membrane-bound or extracellular matrix-associated, exhibits immune regulatory effects in vitro.
- These findings suggest a novel mechanism for immune regulation within the central nervous system.
Abstract:
The brain has long been recognized as an immune privileged site and probably contains multiple immune regulatory factors. We have investigated the immune regulatory properties of brain tissue on cultured lymphocytes. Homogenized brain tissue inhibits proliferation to antigen, but stimulates proliferation in response to most mitogens. The inhibitory activity is destroyed by treatment with proteases or neuraminadase. The activity is in the insoluble fraction of the homogenate, but becomes soluble in 0.04 M NaOH. After gel filtration chromatography of the alkali soluble material, the suppressive activity is in the high molecular weight fraction which contains protein and carbohydrate. The brain homogenate blocks the effects of IL-2. The activity is not affected by neutralizing antibodies against regulatory cytokines, does not depend on Fas or FasL, and is not due to the presence of gangliosides. These data suggest that a brain glycoprotein or proteoglycan which is either membrane-bound or part of the extracellular matrix has immune regulatory effects in culture. The relevance of these findings to immune regulation in the intact animal deserves further investigation.
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